Estradiol and levonorgestrel: effects on bleeding pattern when administered in a sequential combined regimen with a new transdermal patch.

OBJECTIVE: A 1-year, randomized, multicenter study was carried out to assess the effects of estradiol/levonorgestrel, delivered transdermally by 7-day patches in a sequential combined regimen, on bleeding pattern and acceptability in postmenopausal women. METHODS: A total of 468 postmenopausal women were randomized to 15-cm2, 22.5-cm2 or 30-cm2 patches containing 17 beta-estradiol alone (50, 75 or 100 micrograms/24 h, respectively) for 2 weeks followed by 17 beta-estradiol/levonorgestrel (50/10, 75/15 or 100/20 micrograms/24 h) for 2 weeks. RESULTS: The occurrence of cyclic bleeds was dose-dependent, with an increase at higher dosages; the frequency of a cyclic bleed per treatment cycle was 40% in the 50/10 micrograms/24 h patch, 62% in the 75/15 micrograms/24 h patch and 76% in the 100/20 micrograms/24 h patch. The incidence of intermittent bleeding also increased with higher doses, from 22% in the 50/10 group to 35% in the 100/20 group; 20% of women in the 50/10 group did not bleed at all; the corresponding figures for the 75/15 and 100/20 groups were 7% and 0%, respectively. Time of onset of cyclic bleeding was constant in all groups. The mean duration of cyclic bleeding was constant within each group, but increased from 4.4 days in the 50/10 to 6.3 days in the 100/20 group. The regularity and predictability of cyclic bleeding were high in all groups. Recurrence of cyclic bleeds was acceptable for most women (90%). CONCLUSIONS: Sequential combined transdermal 17 beta-estradiol/levonorgestrel shows very good cycle control that is well accepted by postmenopausal women.